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Webbed toes

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Webbed toes

Postby dae » Sun May 04, 2008 8:07 pm

I wasn't quite were to post this (I exhort the moderators to install a developmental biology section), but I know that as an embryo, all limbed vertebrates have webbed fingers and toes. Digit identity is specified by the inter-digital (ID) region posterior to a given digit by a posterior-to-anterior gradient of Sonic Hedge Hog (or orthologous protein).

I.e. the cells in between your index and middle finger confer identity to your index finger, if those cells were prematurely removed your index finger would adopt thumb-identity.

The ID regions eventually undergo apoptosis due to high BMP concentrations, leaving the separated digits.

People who retain the ID regions postnatally have dysfunctional apoptosis pathways. I was curious, then, if there is any evidence that people with webbed fingers and/or toes have increased susceptibility to developing cancer.

Thanks! Theories and speculations are welcomed!
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Postby MrMistery » Mon May 05, 2008 7:19 am

Well, i am not acquainted with the pathway, but i suspect that most likely than not the person has a defective signaling system and would not be able to enter apoptosis induced by bone morpogenetic protein. However, I am guessing that apoptosis in the human body is generally induced through other pathways, such as the NK cells inducing apoptosis.
Of course, if the cells have a defective apoptosis pathway, then he will without doubt be predisposed to cancer.
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Postby dae » Mon May 05, 2008 8:10 am

Yeah, I don't know what genetic defects that lead to this pathway malfunction, or if there's any cross over between them and anti-oncogenic apoptosis pathways.

Just FYI,
BMP activates a TGF{beta} Receptor Ser/Thr Kinase pathway leading to activation of Smad 1,5 which dimerizes with Smad 4 then translocates to the nuclease where it acts as a transcription factor.
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Postby snowcapk » Tue May 06, 2008 10:04 am

People with webbed toes don't have a general deficit in apoptosis: their brains would explode out of their heads long before they got old enough to develop cancer. You've probably seen those pictures of caspase-9 KO embryos. I agree with MrMistery that the defect is probably downstream of a particular BMP signaling pathway. (And there are many, including many ligands, receptors, SMADs, SMAD inhibitors, chordin/noggin, etc. etc.)

Also note that BMP is unlikely to mediate anti-oncogenic apoptosis. BMP is a secreted ligand capable of acting over relatively large distances. If your body used high [BMP] to kill cancerous cells, you would look like swiss cheese: an entire chunk of you would be missing everywhere a single cell had failed to complete DNA repair. Apoptosis is an event that is designed to be confined to the cell that is experiencing it, so it seems unlikely that long-range signals like BMP would mediate apoptosis except when your body is deliberately trying to carve a slice out of itself, as is the case with the tissue between your fingers.
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