Hox Genes PDF

Hox Genes Named after the presence of a homeobox, a specific protein fold that evolved to bind DNA. William Bateson (1894) first described homeotic transformations. He also coined the term HOMEOSIS. HOMEOSIS: the replacement of part of one segment of an insect or other segmented an...

Hox Genes Named after the presence of a homeobox, a specific protein fold that evolved to bind DNA. William Bateson (1894) first described homeotic transformations. He also coined the term HOMEOSIS. HOMEOSIS: the replacement of part of one segment of an insect or other segmented animal by a structure characteristic of a different segment. For example, replacement of a leg with a wing. Homeotic genes were first identified and Homeotic Selector Genes Hom-C complex SPATIAL COLINEARITY: the correspondence between ordering of Hox genes along the chromosome and their expression patterns along the head-tail axis Engrailed: Not a Hox gene but regulated by Hox genes. Plays a role in segment polarity (define the anterior vs posterior of the segment seen above) Antennapedia: A Hox gene Ultrabithorax: A Hox gene Distal-less: Not a Hox gene but regulated by Hox genes. Important for limb development. DLX genes in humans.  Transcription direction 3’ 5’ They are also transcribed “posterior to anterior” in relation to the embryo.  Homeotic Phenotypes Normal fly head Antennapedia mutant Normal fly Ultrabithorax mutant  Alpha (a) helix DNA DNA Minor groove MAJOR groove HOX genes encode members of the homeodomain protein family  Why so many? Functional Redundancy? ransition to Active Chromatin States Determines which HOX Genes are Expressed Brief review of what is transpiring in the posterior region of the embryo as somites are being constructed FGF NMPs going into RA elongating neural tube Source of S0 S1 Neuromesoder S2 mal Progenitors S3 … SN (NMPs) NMPs going into S0: 1st somite formed presomitic S1: 2nd somite formed mesoderm S2: 3rd somite under construction S3 … SN future somites  The shape of the vertebrae will be determined by the HOX genes expressed within Somites will the somite give rise to vertebrae 3’ 5’  Hox c4 Hox c5 Hox c6 Anterior Hox c8 Posterior Hox c9 Hox c10 From: A Combination of Activation and Repression by a Colinear Hox Code Controls Forelimb-Restricted Expression of Tbx5 and Reveals Hox Protein Specificity by Satoko Nishimoto, Carolina Minguillon, Sophie 1 2 3 1 4 5 2 6 3 7 4 8 5 6 9 7 10 11 12 13 Notice that by shifting the boundaries of expression of specific HOX genes, we end up with two distinct vertebral patterns: One for chicken, the other for mouse Shift in this direction is more mouse-like Shift in this direction is more chick-like Norm al Deletion of Hox10a, Hox10c, and Hox10d Mutant WT Figure 25.12 (p 749): 80% of fetuses with extra cervical ribs dies before birth. The survivors often develop cancer early in life. 7.7: Axis regionalization is underway prior to the emergence of vertebrae from s Punch line: Presomitic mesoderm from the region of the embryo that will give rise to thoracic vertebrae (vertebrae with ribs) is specified and determined long before the emergence of the actual ribbed vertebrae. Fig. 17.7: Other Examples of Hox Gene Misexpression Hoxa10 Hoxb6 Hoxa10 HOX genes also regulate proximal to distal patterning A Pr D L R A Di P Pr Di Easy to remember: V A: Anterior (Rostral) Pinky is P: Posterior (Caudal) Posterior P L: Left R: Right Pr: Proximal Di: Distal  HOX Genes in Limb Development Proximal Distal Proximal Distal Humerus Radiu Hand Femur Tibia Foot s& & 9 + 10 Ulna 10 + 11 10 + 11 10 Fibula 10 + 11 + +12 +13 11 + 12 + 12 13 Figure 19.3 (p 574) Mouse Human Almost complete Polysyndactily (many fingers fused) loss of radius & ulna Loss of d13 Loss of d11