Fig. 10.

Model and summary of HOXA3 function in the third pharyngeal pouch at E10.5-E11.5. The box represents the endodermal primordium, with the ventral thymus and dorsal parathyroid domains indicated. In the parathyroid domain (red), HOXA3 represses Fgf8 and p63 expression, and upregulates Tbx1 and Gcm2. Once upregulated, Gcm2 is sufficient to promote parathyroid differentiation and survival independent of HOXA3. In the thymus domain (blue), HOXA3 is required for Bmp4 expression, and potentiates Foxg1 and Foxn1 expression (dashed lines), both of which are delayed in the absence of Hoxa3. Il7 expression is upregulated in Hoxa3^−/− mice. BMP4 has also been implicated in regulating Foxn1 in other studies, although it is not required. We propose that HOXA3 upregulates a thymus-specific survival signal (SS) in both the endoderm and NCC (outside of the box); the receptor for this signal (R-SS) in the endoderm is HOXA3-independent.