Holoprosencephaly (HPE) is a cephalic disorder that occurs during embryonic development. The disorder prevents the normal separation of the frontal lobe (prosencephalon) into 2 separate bilateral hemispheres. In most severe forms, death occurs prior to birth. In some cases, it can prevent normal facial structure from developing resulting in structural abnormalities of the eyes, nose, and lip. The extent of seriousness of holoprosencephaly varies.
The most serious form of HPE is known as alobar holoprosencephaly. Alobar HPE is characterized by no separation in the brain, absent midline structures, and possessing only one ventricle (the lateral and third ventricles are not present). A dorsal cyst is also present in individuals with alobar HPE, …show more content…
The SHH protein is expressed by the SHH gene, the SHH protein (a morphogen) plays a pivotal role in embryogenesis by inducing development by chemical signaling. SHH is important for cell growth, specialization, and patterning of the body. It is also important for brain and spinal cord development (ventral CNS patterning), as well as development of the eyes, limbs, and various other parts of the body. During embryogenesis, SHH is expressed in the notochord, floor plate of the neural tube, brain, gut, and zone of polarizing activity (ZPA) of limbs. In particular, two of the critical structures that SHH induces are the floor plate and neural tube. Both of these structures are critical for central nervous system (CNS) development. The neural tube eventually develops into the brain and spinal cord. Whilst the floor plate serves as structural support for the neural tube and also guides tissues to their designated positions during development. In particular, the floor plate requires a high concentration of SHH to be present during development in order to form and function properly. Roesseler et al. showed that diminished expression of SHH will result in developmental disorders such as HPE. SHH participates in a Sonic Hedgehog-Patched-Gli (SHH-PTCH-GLI) pathway. Dysfunctional regulation of the SHH-PTCH-GLI pathway leads to various human developmental disorders and