Polydactyly Tanner Zocher What is polydactyly Preaxial Postaxial

Polydactyly Tanner Zocher

What is polydactyly? Preaxial Postaxial

What causes polydactyly? GLI 3 Hh

The GLI 3 gene is associated with polydactyly C 2 H 2 zinc finger domains 1580 AA

What are zinc fingers?

What are transcription factors?

GLI 3 is part of the Hedgehog pathway Inactivated io t p i scr No n a r T Activated n cr s n a r T n o i ipt

GLI 3 is highly conserved in… C 2 H 2 zinc finger domains Human 1580 AA Mouse 1583 AA Zebrafish 1553 AA C. elegans 1110 AA Drosophila 1279 AA

What is the phylogenetic relationship?

What is the gap in knowledge? The function of GLI 3 in mediating digit number and placement is unknown.

What is the primary goal? Determine GLI 3’s role in the mechanism controlling digit count and placement

What Model Organism will be used?

How will the primary goal be reached? Aim 1: Aim 2: Aim 3: Disrupt GLI 3 zinc finger domains to link pre- and postaxial polydactyly phenotypes to the disruption of particular loci Identify temporal & local GLI 3 expression during embryogenesis Identify novel protein interactions in wildtype and mutant GLI 3 specimens

How will the primary goal be reached? Aim 1: Aim 2: Aim 3: Disrupt GLI 3 zinc finger domains to link polydactyly phenotypes to the disruption of particular loci Identify temporal & local GLI 3 expression during embryogenesis Identify novel protein interactions in wildtype and mutant GLI 3 specimens

Aim 1: Link peptide domains to polydactyly phenotypes

How will the primary goal be reached? Aim 1: Aim 2: Aim 3: Disrupt GLI 3 zinc finger domains to link pre- and postaxial polydactyly phenotypes to the disruption of particular loci Identify temporal & local GLI 3 expression during embryogenesis Identify novel protein interactions in wildtype and mutant GLI 3 specimens

Aim 2: The where and when of GLI 3 expression Embryogenesis Day 1 Day 2 Day 3 Day 4

How will the primary goal be reached? Aim 1: Aim 2: Aim 3: Disrupt GLI 3 zinc finger domains to link pre- and postaxial polydactyly phenotypes to the disruption of particular loci Identify temporal & local GLI 3 expression during embryogenesis Identify novel protein interactions in wildtype and mutant GLI 3 specimens

Aim 3: Find altered protein interaction patterns GLI 3 Skeletal Development

Conclusions 1. Polydactyly is characterized by the development of additional digits, and is caused by errors in the transcription factor GLI 3 2. GLI 3 has five well-conserved zinc-finger domains, which we hypothesize to be the sequences essential to proper digit number and placement 3. Our goal is to determine the mechanistic role GLI 3 plays in controlling digit count and placement, using Mus musculus as a model organism

Image References Title Slide: https: //radiopaedia. org/cases/polydactyly-5 Slide 1: http: //p 0 lycephaly. blogspot. com/2014/05/growth-evolution-supernumerary-body. html https: //www. handsurgeryresource. com/polydactyly Slide 3: https: //embryology. med. unsw. edu. au/embryology/index. php/Book_-_Human_Embryology_and_Morphology_20 Slide 5: Used with permission from H. Adam Steinberg Slide 7: https: //pediaa. com/how-do-transcription-factors-bind-to-dna/ Slide 8: https: //www. novusbio. com/hedgehogpathway. html Slide 12: https: //sites. nationalacademies. org/cs/groups/pgasite/documents/webpage/pga_049911. pdf Slide 13: https: //fbresearch. org/small-white-mouse-2/ https: //stke. sciencemag. org/content/2/76/ra 29/tab-figures-data Slide 16: https: //www. dailymail. co. uk/health/article-7062053/Girl-born-14 -fingers-undergoes-life-changing-surgery-correct-defect. html https: //www. pbs. org/wgbh/nova/allfours/gene-04. html https: //www. ortho. wustl. edu/content/About-Us/3284/Videos/Dr-Charles-Goldfarb/Extra-Digits-Radial-Polydactyly. aspx Slide 18: http: //www. informatics. jax. org/cookbook/figures/figure 7. shtml https: //www. pdn. cam. ac. uk/research/developmental-biology-and-reproduction

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