Annexe : Cerebellar development

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Questions and Answers

What is the effect of reducing FGF8 in the r1 territory?

  • Expansion of granule cell precursors
  • Loss of the vermis (correct)
  • Reduction of Otx2 expression
  • Expansion of Otx2 expression (correct)

Which layer of the cerebellum is considered a potential site for medulloblastoma?

  • Molecular layer
  • Purkinje cell layer
  • External germinal layer (correct)
  • Internal granule layer

What happens to Otx2 expression when ectopic FGF8 induces cerebellar tissue in the midbrain?

  • It increases slightly
  • It decreases significantly (correct)
  • It increases significantly
  • It stays the same

Which of the following is NOT a key feature of cerebellum development?

<p>Development of the corpus callosum (A)</p> Signup and view all the answers

What process are granule cell precursors involved in, according to the provided information?

<p>Differentiation and radial migration (B)</p> Signup and view all the answers

Which of the following statements accurately describes the role of FGF signalling in cerebellar development?

<p>FGF signalling is not necessary for the formation of the cerebellum but contributes to its growth. (B), FGF signalling is essential for maintaining the Otx2-negative domain in rhombomere 1. (D)</p> Signup and view all the answers

According to the passage, what happens when FGF signalling is blocked in rhombomere 1?

<p>The rhombic lip and rhombomere 1 experience reduced growth. (A)</p> Signup and view all the answers

Based on the information provided, which of the following is NOT a direct consequence of FGF signalling in rhombomere 1?

<p>Directly inducing cerebellar differentiation. (A)</p> Signup and view all the answers

The passage suggests that FGF signalling is...

<p>Involved in both maintaining a specific domain and regulating growth. (B)</p> Signup and view all the answers

What evidence supports the claim that FGF signalling is not directly responsible for the induction of cerebellar differentiation?

<p>The cerebellum develops normally in zebrafish fgf8 mutants when Otx2 expression is rescued. (A)</p> Signup and view all the answers

What is the primary location of granule cell precursor accumulation in the developing cerebellum?

<p>The external germinal layer (C)</p> Signup and view all the answers

During which developmental phase does the granule cell precursor undergo transit amplification?

<p>The third phase, extending into early prenatal life (C)</p> Signup and view all the answers

Which organisms exhibit external migration of granule cells during development?

<p>Metamorphic amphibians, birds, and mammals (D)</p> Signup and view all the answers

What is the primary function of the rhombic lip in cerebellar development?

<p>Establishing the basic dichotomy between GABAergic and glutamatergic cell types (B)</p> Signup and view all the answers

What is the connection between cerebellar development and cognitive function?

<p>Damage to the developing cerebellum can lead to cognitive deficits, including motor dysfunction. (B)</p> Signup and view all the answers

Which of the following is NOT a characteristic of the cerebellar development phase that involves transit amplification?

<p>The rhombic lip plays a significant role in this phase (A)</p> Signup and view all the answers

Which of the following statements accurately describes the difference in granule cell migration between teleosts and mammals?

<p>Granule cells migrate internally in teleosts and externally in mammals (C)</p> Signup and view all the answers

What is the primary outcome of transit amplification in the developing cerebellum?

<p>Exponential increase in the number of granule cell precursors (D)</p> Signup and view all the answers

What is the significance of the rhombic lip in relation to the development of the cerebellum?

<p>The rhombic lip acts as a signaling center that induces the formation of cerebellar granule neurons. (B)</p> Signup and view all the answers

What role does TGFβ signaling play in cerebellar development?

<p>TGFβ signaling promotes the differentiation of cerebellar granule neurons. (B)</p> Signup and view all the answers

What is the primary function of the roof plate in the development of the cerebellum?

<p>It secretes signaling molecules that influence rhombic lip cell differentiation. (A)</p> Signup and view all the answers

Which of the following genes is expressed in the ventricular zone of the cerebellum?

<p>Ptf1a (C)</p> Signup and view all the answers

Which of the following cell types is NOT derived from the ventricular zone of the cerebellum?

<p>Choroid plexus cells (A)</p> Signup and view all the answers

Based on the information provided, what is a defining characteristic of the rhombic lip?

<p>It is a dynamic zone where cells rapidly migrate away after differentiation. (D)</p> Signup and view all the answers

Which of the following cell types is primarily glutamatergic?

<p>Cerebellar granule neurons (A)</p> Signup and view all the answers

Which of these has been demonstrated as impacting granule cell precursor cell cycle length?

<p>MicroRNA 22 (A)</p> Signup and view all the answers

What is the proposed role of "Atonal" in neurogenesis, based on its evolutionary conservation and expression?

<p>A conserved role in neurogenesis (C)</p> Signup and view all the answers

From the provided text, which protein has been shown to regulate cerebellar granule neuron genesis?

<p>Math1 (B)</p> Signup and view all the answers

Which of the following has been implicated in regulating the growth and patterning of the cerebellum?

<p>Sonic Hedgehog (A)</p> Signup and view all the answers

Which of these plays a role in determining the fate of the dorsal mesencephalon versus the cerebellum?

<p>Otx2 (B)</p> Signup and view all the answers

Which of these proteins is known to impact the differentiation of cerebellar neurons?

<p>F3/Contactin (D)</p> Signup and view all the answers

Which of these plays a role in the formation of the cerebellar granule cell layer?

<p>Math1 (B)</p> Signup and view all the answers

Which of these has been shown to be involved in the development of the midbrain-hindbrain boundary?

<p>Grainy head-like 2 (B)</p> Signup and view all the answers

What is a key distinguishing feature of the amphibian cerebellum that sets it apart from other tetrapod cerebellums?

<p>The amphibian cerebellum does not form a sub-pial granule layer at metamorphosis. (D)</p> Signup and view all the answers

What triggers the inward migration of post-mitotic granule cells in the amphibian cerebellum?

<p>Thyroid hormone. (D)</p> Signup and view all the answers

What is the transient feature of the developing cerebellum in both birds and mammals?

<p>The external granule layer (EGL). (A)</p> Signup and view all the answers

What observation is crucial for understanding the evolution of the cerebellum and its connection to ASD (Autism Spectrum Disorder)?

<p>The significant role of cerebellar connectivity in ASD. (C)</p> Signup and view all the answers

What is the primary focus of the research discussed in the given text regarding the cerebellum?

<p>The functional diversity of cerebellar neuronal subtypes. (A)</p> Signup and view all the answers

What is the significance of the difference between amphibian and amniote cerebellar development, particularly regarding the role of Neurod1?

<p>It highlights the evolutionary divergence in cerebellar developmental mechanisms. (B)</p> Signup and view all the answers

What is the key question raised by the observation regarding the EGL in amphibians?

<p>Whether the EGL originally had a primary role in proliferation or served other developmental functions. (A)</p> Signup and view all the answers

The text suggests that the cerebellar development of different species differs in all the following aspects EXCEPT?

<p>The timing of metamorphosis. (D)</p> Signup and view all the answers

Flashcards

FGF Signaling

A signaling pathway involved in growth and maintenance of brain structures.

Cerebellum Rescue

Restoration of cerebellum function in zebrafish using specific signaling pathways.

Otx2 Expression

A transcription factor important for specifying brain regions, especially in early development.

Rhombomere 1 (r1)

The most anterior segment of the hindbrain in vertebrate embryos, crucial for brain development.

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Rhombic Lip Growth

A structure in the developing hindbrain that gives rise to important neural populations.

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Granule cells

Neurons in the cerebellum that process information and connect with Purkinje cells.

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Purkinje cells

Large neurons in the cerebellum that regulate motor coordination and cognitive functions.

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Rhombic lip

Structure in the developing brain that gives rise to granule cell precursors.

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Cerebellum functions

Involved in both motor control and higher cognitive functions, beyond just coordination.

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Cognitive impairment

Deficiencies in mental processes like memory and reasoning often linked to cerebellar damage.

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Preterm cerebellar damage

Early damage to the cerebellum that can lead to long-term cognitive deficits and motor issues.

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Vermal agenesis

Congenital condition where part of the cerebellum is absent, leading to disorders.

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ASD and cerebellar disruptions

Studies show structural brain abnormalities in mouse models of autism linked to cerebellar changes.

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Otx2

A transcription factor that regulates brain and cerebellum development.

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External Germinal Layer (EGL)

An outer layer in the cerebellum involved in granule cell precursor generation.

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Medulloblastoma

A malignant pediatric brain tumor originating from the cerebellum.

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Vermis

The central part of the cerebellum that plays a key role in motor control.

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EGL

External Granule Layer; a transient layer during cerebellar development.

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Granule Cell Differentiation

Process by which undifferentiated cells become granule neurons.

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Thyroid Hormone Role

Triggers inward migration of post-mitotic granule cells in amphibians.

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Cellular Diversity

Variety of neuron types generated in the cerebellum during development.

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Atoh1-positive Cells

Cells expressing Atoh1, crucial for granule cell differentiation.

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Metamorphosis

The process of transformation from larval to adult stage in amphibians.

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Progenitor Zones

Regions where progenitor cells reside, crucial for brain development.

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Cerebellar Connectivity

Connections between neurons in the cerebellum affecting functionality.

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TGFβ signals

Signals secreted from neighboring cells that induce transit in development.

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Atoh1

A gene crucial for the development of glutamatergic neurons from the rhombic lip.

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Delta-Notch signaling

A communication system important for determining cell fate during development.

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Ventricular Zone

A layer in the developing brain where progenitor cells proliferate.

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Ptf1a

A transcription factor expressed in the cerebellar ventricular zone related to GABAergic interneurons.

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Roof Plate

Structure that contains non-neural lineage cells and contributes to the choroid plexus.

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Glutamatergic Cells

Neurons that predominantly use glutamate as their neurotransmitter.

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CNS Dorsal Midline Cells

Cells involved in the formation of the choroid plexus epithelium.

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bHLH Protein

Basic Helix-Loop-Helix protein important for neural development and gene expression.

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Sonic Hedgehog

A signaling molecule that regulates growth and patterning in the cerebellum.

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MicroRNA 22

A microRNA that regulates cell cycle length in cerebellar granular neuron precursors.

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Grainy Head-like 2

A protein that regulates midbrain-hindbrain boundary development.

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Neurogenesis Modulation

The process by which external factors influence the development of new neurons.

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Study Notes

Cerebellum Development

  • The cerebellum is a crucial model for studying neurogenesis and circuit assembly.
  • Its role in higher cognition and various disorders highlight its importance in numerous fields.
  • Recent studies have refined understanding of cerebellar development, including its territorial allocation, transit amplification, and neuronal diversity generation.
  • These aspects are regulated by distinct mechanisms, affecting health and disease.

Key Aspects of Cerebellar Growth

  • Cerebellar Anlage Allocation: Territory for cerebellum is allocated early in embryonic development, near the hindbrain-midbrain boundary.
  • Transit Amplification: Granule cell precursors, generated from the rhombic lip, proliferate extensively in the external germinal layer (EGL), significantly expanding their numbers. This process is less apparent in aquatic vertebrates.
  • Neuronal Diversity: Factors regulating cerebellar cell diversity are critical. GABAergic and glutamatergic progenitors arise in specific regions and stages.
  • Molecular Boundaries: Key genes like Otx2 and Hoxa2 define the limits of cerebellar territory, and Gbx2 influences differentiation. FGF signaling helps maintain these boundaries and is crucial for vermis development.
  • FGF Signaling: FGF8, from the isthmus, is important in cerebellar development. It influences the size of the cerebellar anlage, but downregulation is crucial for cell type specification.
  • External Germinal Layer (EGL): Transient zone with proliferating granule cell precursors, which is essential for transit amplification crucial for cerebellum development and in medulloblastomas. The EGL is crucial for the generation of granule cells.
  • Timing and Diversity: A specified timeline regulates cell production in the rhombic lip. Granule cells appear after other cell types. The development of cerebellar nuclei follows distinct stages and has evolutionary differences in species.

Diseases and Disorders

  • Medulloblastoma: A pediatric cancer arising from the cerebellum or brainstem. Disruption of transit amplification/EGL is a model for medulloblastomas. Other pathways like Wnt signaling also might play a role depending on the subtype.
  • Autism Spectrum Disorder (ASD): Cerebellar damage may contribute to ASD. Anatomical deficits in the cerebellum are often linked to ASD, including issues with folia and cell types (like Purkinje cells).
  • Cognitive Deficits: Cerebellar dysfunction can result in cognitive impairments. Early disruption of patterning could create later cognitive impairment.

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