Neurulation Part II Bio361 PDF

After neurulation – the brain Hindbrain Midbrain r1, r2, etc.: Forebrain Metameric structures in the hindbrain are known as rhombomeres Branchial (BA#) aka...

After neurulation – the brain Hindbrain Midbrain r1, r2, etc.: Forebrain Metameric structures in the hindbrain are known as rhombomeres Branchial (BA#) aka pharyngeal arches Guthrie (2007) Nat Rev Neuro 8:859-871 Wall Cavity Forebrain (Prosencephalon) Future retina Midbrain (Mesencephalon) Hindbrain (Rhombencephalon) Figure 13.16 Early brain development and formation of the first brain chambers (Part 2) Somites Stage 8+ Stage 10+ Constriction of the posterior neural tube allows brain ventricles to form 24 hpf 30 hpf Embryonic origins of adult brain structures ral Cereb es ph e r Hemis Temperature Hunger Attachment behaviors Thirst Fatigue Sleep Circadian rhythms. Retina Hypo thala mus Cerebe llum Medulla Motor control o blongat a Breathing Heart rate Blood pressure  Alternating domains of ephrin and ephrin receptor expression. This leads to rhombomere formation in primitive hindbrain Ephrin Eph R From fuzzy boundaries To crisp boundaries Ephrin and ephrin receptor (Eph R) function as a chemorepulsive pair Lumsden, A (1999) Nat. Cell Bio. 1:E83-E85 EphR: erythropoietin-producing human hepatocellular receptors Cell A Ephrin A & B are “ligands” Cell B (tyrosine kinase)  Bidirectional ephrin signaling leads to boundary formation JUXTACRINE INTERACTION Activation of the ephrin receptor (by binding to the ephrin ligand) results in increase tyrosine kinase-mediated phosphorylation in the receptor-containing its movement away from the ligand.  KROX20 expression is used as a marker of rhombomere boundary formation Eph4A EphrinB2A Eph4A + EphrinB2A Control Morpholino Morpholino Morpholino Note the crisp boundaries Notice that when EphA4 is Notice that when Notice that when both of KROX20 knocked down, the EphrinB2A is knocked EphA4 and Ephrin B2 are boundaries of KROX20 down, the boundaries of knocked down, the become fuzzy KROX20 aren’t that fuzzy boundaries of KROX20 become super fuzzy and bleed into each other Conclusion: EPH4A is required for rhombomere boundary formation  Rhombomeres exhibit differential gene expression Technique: In situ hybridization (showing mRNA expression only)  Dorsal-Ventral axis of the nervous system D Sensory neurons V V Motor neurons V Sensory neurons: Arrive on the dorsal side Motor neurons: Leave through the ventral side  Dorsal-Ventral axis of the nervous system BMP and SHH are the morphogens that initially pattern the DV axis of the nervous system  Dorsal-Ventral axis of the nervous system Note that the BMP and SHH gradients are illustrated by different shading Dorsal-Ventral axis of the nervous system BMP  Dorsal-Ventral axis of the nervous system D Transcription Factors Dorsalin Pax7 Pax6 Region of motor neuron specification (Olig2 Expression) Nkx6.1 Shh Notochord V Dorsalin: A member of the BMP pathway Gilbert 8th Ed., Fig. 9.13 Figure 13.19 Dorsal-ventral specification of the neural tube (Part 3) Pax7 Pax6 Nkx6.1 Figure 13.20 Notochord-derived Shh induces ventral neural tube structures INDUCTIVE PROPERTIES OF THE NOTOCHORD Figure 13.18 Neural tube gene expression responds to both concentration and duration of Shh (Part 1) Figure 13.18 Neural tube gene expression responds to both concentration and duration of Shh (Part 2) Figure 13.22 Transcriptional cross-repression in neural progenitor cells hph: hours post headfold formation hpe: hours post-electroporation Model for interpreting the Shh morphogen gradient Notice how Shh gradient is “moving” from Ventral to Dorsal. Shh is secreted and diffuses through the extracellular matrix. the developing caudal region of the spinal cord. All axes are established. RP: Roof plate (top of neural tube) FP: Floor plate (bottom of neural tube) Note that the NMPs (neuralmesodermal progenitors) are a source of neural cells (Middle path) and mesodermal cells (Upper and Lower paths).