Waxman Lab

The ultimate goal of our research is to understand the mechanisms that determine organ size through selection of progenitor cells. Proper determination of organ size is crucial for normal organ form and function, and specification of organ progenitors seems to depend on a balance of inductive and restrictive signals. We currently understand much less about the signals that limit cardiac progenitor specification compared to the signals that promote cardiac progenitor formation. Therefore, our studies are focused on the signals that restrict the size of the cardiac progenitor field.

Signaling Pathways Restrict Size of Heart

We are interested in understanding the mechanisms by which different signaling pathways restrict cardiomyocyte formation. One of the few pathways that has been shown to restrict the size of the heart is retinoic acid (RA) signaling. Inhibition of RA signaling leads to the specification of more cardiomyocytes in vertebrates. We are investigating what genes downstream of RA signaling are involved in restricting the number of cells in the heart and are exploring the mechanisms by which novel mutations affect RA signaling’s ability to restrict cardiac cell number.

Mechanisms Determining Individual Chamber Identity

We are interested in understanding what determines the fates of cells in individual heart chambers. Our research revealed that hoxb5b is required to specifically restrict the number of atrial cells. This suggests that there are factors that may determine individual chamber identity. We seek to understand the mechanisms downstream of hoxb5b that restrict atrial cell number, characterizing a novel mutant that may specifically affect atrial size and identifying factors that restrict ventricular cell number.