BDRC SEMINAR SERIES
Malcolm Logan
King’s College London
Friday 4th March 2016 1pm – 2pm
Levinsky Room
Abstract
Uncovering the mechanisms of vertebrate limb development and origins of congenital limb defects
We are interested in understanding the mechanisms that regulate limb development and how
disruption of these events contributes to the aetiology and pathology of congenital limb
abnormalities. For many years we have studied Holt-Oram Syndrome (HOS), a dominant disorder
associated with characteristic upper limb defects that present with highly variable penetrance. We
have used a combination of genetic approaches in the mouse to model HOS. By conditionally
deleting Tbx5 at different time points during limb development and in different limb tissues, we
have uncoupled several characteristic features of the presentation of the limb defects. I will discuss
our latest work deciphering the function of the Tbx5 protein, how expression of the gene is
regulated in the limb and how these both relate to clinical presentation of HOS.
BioSketch
I first began studying vertebrate limb development as a postdoc in the lab of Cliff Tabin at Harvard
Medical School. It was during this time I began to use chick and mouse model systems to study the
function of members of the T-box and paired-type homeodomain family transcription factors in
regulating aspects of limb development and other aspects of embryogenesis.
At the end of 2000, I started by independent group at NIMR, Mill Hill. Our work has focused on
addressing two fundamental questions: How the cells that form the early limb bud are recruited
from the embryo flank and how limb bud progenitors are organised into distinct limb tissues. We
have continued to use experimental tool kits available in both chick and mouse models and have
also used zebrafish and Xenopus when we have found it appropriate.
At the end of 2013 my group moved to The Randall Division, King's College London. Here we have
continued our work on limb bud induction and initiation and regulation of limb tissue
morphogenesis with a particular emphasis on understanding how this can explain the aetiology and
pathology of congenital limb abnormalities. We are exploiting our proximity to Guy's and St Thomas'
and GOS hospitals to develop collaborative projects with colleagues in the departments of clinical
genetics, plastics and orthopaedics.