Development of an Adult Body Plan PDF

Development of an Adult Body Plan BIO 130 LEC INTARMED 2030 | Prof. Bordallo/Leonardo | LU2 SEM 1 | SY. 2023-2024 About 10 hours after fertilization: Segmentation p...

Development of an Adult Body Plan BIO 130 LEC INTARMED 2030 | Prof. Bordallo/Leonardo | LU2 SEM 1 | SY. 2023-2024 About 10 hours after fertilization: Segmentation pattern is clearly established: T1-T3 for thoracic TABLE OF CONTENTS segments, A1-A8 for abdominal segments, Acron for I. Overview of Drosophila Development head-forming region A. Early Stages of Embryonic Structures have developed in adult fly Development II. Specification of Anterior-Posterior Axis II. SPECIFICATION OF ANTERIOR-POSTERIOR AXIS A. Maternal Effect Genes a. Egg Chamber of Drosophila Maternal effect b. Maternal Protein Gradient ➔ occurrence when offspring’s phenotype for a trait c. Terminal Genes is controlled by nuclear gene products in the III. Segmentation in the Early Embryo unfertilized egg A. Zygotic Genes ◆ nuclear genes in female gamete are a. Segmentation Genes transcribed b. Homeotic Genes (Hox) ◆ genetic products from transcription accumulate in cytoplasm ◆ upon fertilization, genetic products are I. OVERVIEW OF DROSOPHILA DEVELOPMENT distributed and influence patterns of early development ➔ genotype of female parents determine the phenotype of offspring EARLY STAGES OF EMBRYONIC DEVELOPMENT MATERNAL EFFECT GENES Genes that are expressed into mRNA and/or proteins in the mother that direct the early development of the offspring Encode transcription factors, receptors, and proteins that regulate expression of zygotic genes EGG CHAMBER OF DROSOPHILA ______________________________________________________ Figure 1: Early stages of embryonic development of Drosophila After fertilization: Diploid zygote nucleus is produced by fusion of parental gamete nuclei Nine rounds of nuclear divisions produce multinucleated syncytium / syncytial blastoderm Figure 2: Egg chamber of Drosophila (single cell w/ many nuclei within a common cytoplasm) Oogonium divides by mitosis by four times with About 2.5 hours after fertilization: Nuclei migrate to incomplete cytokinesis to produce 16 interconnected the periphery / cortex of the egg and approximately germline cells (15 nurse cells and 1 oocyte four further divisions occur. Pole cells (precursor to precursor) germ cells) form at the posterior pole ○ Nurse cells - produce mRNAs and proteins and About 3 hours after fertilization: Nuclei become transported to the developing oocyte enclosed in membrane, forming a single layer of cells Express maternal genes over embryo surface, creating the syncytial Protein products signal follicle cells to blastoderm differentiate into posterior follicle cells BIO 130 LEC LU 2 SEM 1 | IMED 2030 Page 1 of 6 SAMSON, SDA; MUSA, GS; ALMANDRES, JAS, MATIAS, HAN; REYES, JCDC Development of an Adult Body Plan BIO 130 LEC INTARMED 2030 | Prof. Bordallo/Leonardo | LU2 SEM 1 | SY. 2023-2024 Posterior follicle cells send signals back to the oocyte to organize its microtubules Egg chamber consists of the 16 germline cells + uncommitted polar follicle cells MATERNAL PROTEIN GRADIENT ______________________________________________________ Initiate the formation of the anterior-posterior axis Cytoplasmic polarity (maternal effect) - the lighter the shade, the lesser the concentration of maternal effect genes Figure 5: Diffusion of nanos mRNAs to the posterior end of the oocyte mRNAs that do not reach the posterior end are bound by translation inhibitors and are eventually degraded Figure 3: Cytoplasmic polarity gradient Two maternal mRNAs / morphogens (determine the fate of a cell by their concentration) initiate formation of the A-P axis: ○ Bicoid mRNAs head / anterior morphogen transported actively along microtubules to the anterior end of the oocyte by Dynein protein Figure 6: Different morphogen concentrations determining fate of cell Experiment: Addition of bicoid mRNA to embryos ○ Wild-type embryo - has bicoid gene; forms anterior portion ○ Mutant embryo - no bicoid gene; forms two tail Figure 4: Transport of bicoid mRNAs to the anterior end of portions the oocyte ○ Nanos mRNAs tail / posterior morphogen diffuse passively to the posterior pole of the oocyte and anchored by proteins Figure 7: Body plan development in the addition of bicoid mRNA to wild-type and mutant embryos BIO 130 LEC LU 2 SEM 1 | IMED 2030 Page 2 of 6 SAMSON, SDA; MUSA, GS; ALMANDRES, JAS, MATIAS, HAN; REYES, JCDC Development of an Adult Body Plan BIO 130 LEC INTARMED 2030 | Prof. Bordallo/Leonardo | LU2 SEM 1 | SY. 2023-2024 ○ Addition to anterior end of mutant - normal ○ Acron - terminal portion of the head body plan development ○ Telson - extreme posterior end (tail) ○ Addition to middle of mutant - development of two tails in both ends and formation of head in III. SEGMENTATION IN THE EARLY EMBRYO the middle ○ Addition to posterior end of wild-type embryo (Non-mutant, natural phenotype of a species) - Segmentation in the early embryo consists of a development of two heads sequence of gene expression events that are regulated spatially and temporally. Hunchback and caudal mRNAs are also important for the A-P posterior patterning of the body plan ZYGOTIC GENES ______________________________________________________ Genes transcribed in the embryonic nuclei formed after fertilization Their differential transcription is regulated by the distribution of the maternal effect proteins Figure 8: Concentration of four maternal mRNAs in the anterior and posterior end Hunchback and caudal mRNAs are present at a constant level in both ends and is regulated by bicoid and nanos proteins ○ Hunchback mRNA - Expression is activated by bicoid protein; translation is inhibited by nanos protein Figure 10: Hierarchy of genes in the establishment of the ○ Caudal mRNA - translation is inhibited by bicoid body plan in Drosophila protein; activate zygotic genes important in the formation of the abdomen Figure 9: Four maternal protein gradients in the early embryo TERMINAL GENES ______________________________________________________ Encode proteins that generate the unsegmented Figure 11: Progressive restriction of cell fate during extremities development BIO 130 LEC LU 2 SEM 1 | IMED 2030 Page 3 of 6 SAMSON, SDA; MUSA, GS; ALMANDRES, JAS, MATIAS, HAN; REYES, JCDC Development of an Adult Body Plan BIO 130 LEC INTARMED 2030 | Prof. Bordallo/Leonardo | LU2 SEM 1 | SY. 2023-2024 Maternal effect genes regulate the expression of the first three groups of zygotic genes: gap genes, pair-rule genes, and segment polarity genes ○ These three groups are called segmentation genes. ○ Products of segmentation genes are transcription factors that activate homeotic genes SEGMENTATION GENES ______________________________________________________ Segmentation genes are the first set of zygotic genes Divide the embryo into a series of segments Figure 13: Gap gene expression in Drosophila (hunchback protein in orange, Kruppel in green, yellow has both) ➔ Pair-rule genes ◆ Activated by products of gap genes and maternal-effect genes ◆ Mutations in these genes affect every other segment – a specific part of the affected segment is deleted ◆ Their expression creates a pattern of 7 bands perpendicular to the anterior-posterior axis, dividing the embryo into even smaller regions ◆ Encode transcription factors that activate the Figure 12: Segmentation genes in Drosophila segment polarity genes [NOTE: classification of hunchback and caudal genes varies depende sa source so di na raw natin siya iclaclassify basta alam yung function] ➔ Gap genes ◆ First to be activated ◆ Their expression in specific regions of the embryo divides the embryo into broad regions (head, thorax, and abdomen) ◆ Mutations in these genes result in deletions of segments producing gaps in the normal embryonic body plan (e.g., hunchback mutants lack head and thorax structures) ◆ Activated or inhibited by transcriptions factors encoded by maternal-effect genes ◆ Encode transcription factors that activate pair-rule genes Figure 14: Pair-rule gene expression in Drosophila ➔ Segment polarity genes ◆ Mutations in these genes show defects in every segment ◆ Their expression is regulated by transcription factors encoded by pair-rule genes ◆ Divides the embryo into 14 segments BIO 130 LEC LU 2 SEM 1 | IMED 2030 Page 4 of 6 SAMSON, SDA; MUSA, GS; ALMANDRES, JAS, MATIAS, HAN; REYES, JCDC Development of an Adult Body Plan BIO 130 LEC INTARMED 2030 | Prof. Bordallo/Leonardo | LU2 SEM 1 | SY. 2023-2024 Figure 15: Segment polarity gene expression in Drosophila ➔ The products of the gap, pair-rule, and segment polarity genes work together in the regulation of expression of the homeotic selector genes. HOMEOTIC SELECTOR (HOX) GENES ______________________________________________________ Hox genes are the second set of zygotic genes Figure 17: Changes in the body segments of homeotic Encode transcription factors that regulate the mutants expression of genes involved in the formation of ➔ In organisms with mutations in Hox genes structures (homeotic mutants), the identities of body segments may change. ◆ Third thoracic segment may be transformed into another second thoracic segment ◆ Example: fly with two pairs of wings instead of one pair; head may bear a pair of legs instead of a pair of antennae ➔ Present in genomes of all animals Common properties of Hox genes across different species ➔ Homeobox: a 180-base-pair nucleotide that encodes the homeodomain, a 60-amino acid DNA-binding region Figure 16: Hox genes regulation of gene expression ◆ Conserved in the animal kingdom ➔ Homeodomain: DNA-binding region of the Hox Control development along the anterior-posterior protein axis and the formation of appendages Expression of Hox genes is colinear with the anterior Determine and specify the adult structures to be to posterior organization of the body formed by each segment in the embryo ○ 3’ end genes are expressed at the anterior end ○ 1st thoracic segment = pair of legs ○ Genes in the middle are expressed in the middle ○ 2nd thoracic segment = pair of legs + pair of the embryo of wings ○ 5’ end genes are expressed at the posterior end ○ 3rd thoracic segment = pair of legs + pair of balancers called halteres BIO 130 LEC LU 2 SEM 1 | IMED 2030 Page 5 of 6 SAMSON, SDA; MUSA, GS; ALMANDRES, JAS, MATIAS, HAN; REYES, JCDC Development of an Adult Body Plan BIO 130 LEC INTARMED 2030 | Prof. Bordallo/Leonardo | LU2 SEM 1 | SY. 2023-2024 Figure 18: Synpolydactyly in humans Figure 18: Collinearity of Hox genes and the A-P organization SEGMENTATION GENES IN MICE AND HUMANS ______________________________________________________ Runt ➔ A pair-rule gene in Drosophila ➔ Encodes a transcription factor (runt protein) ➔ Runt domain: a DNA-binding region with 128 amino acids in the runt protein that is conserved in Drosophila, mouse and humans (RUNX2 in humans) ➔ In Drosophila, runt functions in sex determination and nervous system formation ➔ In humans and mice, runt functions in bone formation Cleidocranial dysplasia (CCD) ➔ Result of mutations in RUNX2, characterized by presence of a hole in the skull and underdeveloped or absent clavicles HOX GENES AND HUMAN GENETIC DISORDERS ______________________________________________________ Hox genes in humans ➔ Occurs in four clusters: HoxA , HoxB, HoxC, HoxD ➔ HoxA (in chromosome 7), HoxB (in chromosome 17), & HoxC and HoxD (in chromosome 12) Synpolydactyly (SPD) ➔ Result of mutations in HoxD ➔ syn = “fusion” & poly = “many” ➔ Characterized by extra fingers and toes and abnormalities in bones of the hands and feet BIO 130 LEC LU 2 SEM 1 | IMED 2030 Page 6 of 6 SAMSON, SDA; MUSA, GS; ALMANDRES, JAS, MATIAS, HAN; REYES, JCDC