Notch and Hedgehog in the thymus/parathyroid common primordium: Crosstalk in organ formation

•Notch is required for thymic epithelium specification.•Notch positively regulates parathyroid epithelium differentiation.•Hh positively regulates Gata3/Gcm2/parathyroid-fate domain.•Hh positively regulates Lfng-domain in the 3/4PP.•Hh establishes the dorsal/posterior boundary of Foxn1/thymic rudiment.

The avian thymus and parathyroids (T/PT) common primordium derives from the endoderm of the third and fourth pharyngeal pouches (3/4PP). The molecular mechanisms that govern T/PT development are not fully understood. Here we study the effects of Notch and Hedgehog (Hh) signalling modulation during common primordium development using in vitro, in vivo and in ovo approaches. The impairment of Notch activity reduced Foxn1/thymus-fated and Gcm2/Pth/parathyroid-fated domains in the 3/4PP and further compromised the development of the parathyroid glands. When Hh signalling was abolished, we observed a reduction in the Gata3/Gcm2- and Lfng-expression domains at the median/anterior and median/posterior territories of the pouches, respectively. In contrast, the Foxn1 expression-domain at the dorsal tip of the pouches expanded ventrally into the Lfng-expression domain. This study offers novel evidence on the role of Notch signalling in T/PT common primordium development, in an Hh-dependent manner.