Hamdi-Roze H, Ware M, Guyodo H, et al. - This research was sought to assess the correlation between sonic hedgehog (SHH) and NOTCH signaling to ascertain the mechanism by which NOTCH dysfunction could cause midline malformations of the forebrain. Researchers applied a chemical inhibition method in the chick model and a genetic approach in the mouse model. They also recorded outcomes collected from the clinical diagnosis of a cohort composed of 141 holoprosencephaly patients. These outcomes served new insights into molecular mechanisms underlying the extreme phenotypic variability found in human holoprosencephaly. They exhibited how haploinsufficiency of the SHH and NOTCH activity could contribute to specific congenital hypopituitarism that was correlated with a sella turcica defect.