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PATTERN FORMATION
This document outlines a course on developmental biology and teratology. It discusses how pattern formation during embryogenesis is genetically controlled and involves cells responding to morphogen gradients and cell signaling pathways to develop spatial patterns. Key genes involved in pattern formation are homeobox genes, which help specify where anatomical structures will develop. In particular, Hox genes are organized in clusters and control patterning along the anteroposterior body axis. Mutations in genes of pattern formation can lead to various clinical congenital malformations and anomalies.
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PATTERN FORMATION
- 1. ANA 801 -DEVELOPMENTAL BIOLOGY AND TERATOLOGY BY ADESEJI WASIU ADEBAYO UMAR BUKOLA
- 2. OUTLINE 2 ď‚— INTRODUCTION ď‚— GENESOF PATTERN FORMATION ď‚— CLINICAL IMPORTANCE ď‚— CONCLUSION ď‚— REFERENCES
- 3. INTRODUCTION 3 ď‚— In simpleterms, pattern formation refers to the generation of complex organizations of cell fates in space and time. ď‚— During embryogenesis, information encoded in the genome is translated into cell proliferation, morphogenesis, and early stages of differentiation. ď‚— Embryonic pattern arises from the spatial and temporal regulation and coordination of these events.
- 4. INTRODUCTION 4 ď‚— In developmentalbiology, pattern formation describes the mechanism by which initially equivalent cells in a developing tissue in an embryo assume complex forms and functions (Ball, 2009) ď‚— The process of embryogenesis involves coordinated cell fate control (Lai, 2004; Tyler and Cameron, 2007). ď‚— Pattern formation is genetically controlled, and often involves each cell in a field sensing and responding to its position along a morphogen gradient, followed by short distance cell-to-cell communication through cell signaling pathways to refine the initial pattern. ď‚— In this context, a field of cells is the group of cells whose fates are affected by responding to the same set positional information cues. This conceptual model
- 5. Why Pattern Formation? 5 ď‚—The reliable development of highly complex organisms is an intriguing and fascinating problem. The genetic material is, as a rule, the same in each cell of an organism. How do then cells, under the influence of their common genes, produce spatial patterns ? ď‚— Development of an organism is, of course, under genetic control but the genetic information is usually the same in all cells. ď‚— A crucial problem is therefore the generation of spatial patterns that allow a different fate of some cells in relation to others ď‚— (Koch and Meinhardt, 1994).
- 6. DEFINITION OF TERMS 6 ď‚—Induction is the stimulation of a cell to differentiate in response to a stimulus produced by another cell. It is mediated by inducer substances that diffuse from one cell to another. It results in cell determination. ď‚— Determination is the commitment of a cell to undergo differentiation. It is an irreversible process but is not accompanied by morphological changes. ď‚— Determinants are the cytoplasmic effector molecules that mediate determination. ď‚— Differentiation is the variation in the pattern of expression of a common set of genes to form cells of diverse morphology and function.
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- 11. Time-table of landmarksin early human development 11 ď‚— Day 1 - cleavage ď‚— Days 2-4 - morula; free- floating conceptus in uterine tube ď‚— Days 5-6 - formation of the blastocyst and embryoblast; ď‚— - implantation ď‚— Week 2 (days 7-14) ď‚— - formation of the bilaminar embryo 0.1 mm ď‚— Week 3 (days 15-20) - formation of the trilaminar embryo 1.0 mm ď‚— Week 4 (days 21-28) ď‚— Day 21 - formation of neural tube 2.0 mm ď‚— Day 22 - formation of the heart ď‚— Day 23 - formation of eye and ear rudiments ď‚— Day 25 - formation of branchial arches ď‚— Day 26 - formation of upper limb bud ď‚— Day 28 - formation of the lower limb bud 5.0 mm ď‚— Weeks 5 to 9 (2nd month) - Period of organogenesis ď‚— Week 6 1.0 cm ď‚— Week 9 4.0 cm
- 12. GENES OF PATTERN FORMATION 12 ď‚—Every organism has a unique body pattern. ď‚— This patterning is controlled and influenced by the HOMEOBOX genes. ď‚— These specify how different areas of the body develop their individual structures, e.g. Arms, legs etc.
- 13. HOMEOBOX GENE 13 ď‚— Homeoticgenes are regulatory genes that determine where certain anatomical structures, such as appendages, will develop in an organism during morphogenesis. ď‚— The expression of homeotic genes results in the production of a protein (homeodomain) that can turn on or switch off other genes. ď‚— This genes act as Transcription factors.
- 14. HOX GENE 14 Human hoxgenes are collected into homeotic clusters. o There are 4 homeotic clusters, labelled A,B,C and D, oEach cluster is situated on a different chromosome. o Each homeotic cluster consists of 13 homeotic
- 15. The RNA expressionpattern of three mouse Hox genes in the vertebral column of a sectioned 12.5-day-old mouse embryo: the anterior limit of each of the expression pattern is different Each Hox gene is expressed in a continuous block beginning at a Specific anterior limit and running posteriorly to the end of the developing vertebral column
- 16. HOX GENE 16 The fournumerically corresponding genes for the four different clusters form a paralogous group. o The hox genes are responsible for patterning along the antero-posterior axis. o The genes are expressed sequentially beginning with the paralogous group 1, which is expressed first o The sequential genes specify different segments in cranio-caudal sequence extending from paralogous group 1, which specifies the most cranial structures, to paralogous group 13, which specifies the most caudal structures. o Thus the first genes to be expressed specify the most cranial structures while the last to be expressed specify the most caudal structures. This is responsible for the cranio-caudal sequence of development, where the more cranial segments develop slightly before the more caudal structures. Consequently the upper limb develops ahead of the lower limb.
- 17. Clinical Correlates 17 ď‚— Mutationsin genes of pattern formation leads to a lot of clinical important congenital malformations and anomalies ď‚— Aniridia ď‚— Synpolydactyly ď‚— Axenfeld-Rieger syndrome ď‚— Branchiootorenal syndrome ď‚— Coloboma ď‚— Langer mesomelic dysplasia ď‚— LĂ©ri-Weill dyschondrosteosis ď‚— Microphthalmia ď‚— Mowat-Wilson syndrome ď‚— Amelia ď‚— Limb deformities
- 18. Synpolydactyly 18 Mutation in theHOX D13 gene.
- 19. Aniridia 19 Aniridia with PAX6gene mutation.
- 20. Axenfeld-rieger syndrome 20 mutations inone of the genes known as PAX6, PITX2 and FOXC1.
- 21. REFERENCES 21 • A. J.Koch and H. Meinhardt (1994). Biological Pattern Formation : from Basic Mechanisms to Complex Structures. Rev. Modern Physics 66, 1481-1507 • Ball, (2009). Shapes, pp. 261–290. • Eric C. Lai (2004). "Notch signaling: control of cell communication and cell fate" 131 (5). pp. 965–73. doi:10.1242/dev.01074 • Melinda J. Tyler, David A. Cameron (2007). "Cellular pattern formation during retinal regeneration: A role for homotypic control of cell fate acquisition". Vision Research 47 (4): 501–
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Editor's Notes
- #10  time-table of  landmarks in early human development Day 1           - cleavage Days 2-4       - morula; free-floating conceptus in uterine tube Days 5-6       - formation of the blastocyst and embryoblast;                    - implantation Week 2 (days 7-14)                             - formation of the bilaminar embryo      0.1 mm Week 3 (days 15-20)                    -formation of the trilaminar embryo       1.0 mm Week 4 (days 21-28) Day 21         - formation of neural tube                     2.0 mm Day 22         - formation of the heart Day 23         - formation of eye and ear rudiments Day 25         - formation of branchial arches Day 26         - formation of upper limb bud Day 28         - formation of the lower limb bud          5.0 mm Weeks 5 to 9 (2nd month) - Period of organogenesis Week 6                                                         1.0 cm Week 9                                                         4.0 cm End of embryonic period