Thickening of the ectoderm, which is known as the otic placode
, constitutes the embryological basis of the IE.
The protrusion forms in the dorsal wall of the aortic sac, which has a core derived from the second heart field, with only its outer layer derived from the cardiac neural crest, which is defined as the neural crest residing between the otic placode
and the third somite.
Similarly, lens formation begins in the third week of gestation as the "lens placode
" and initial development concludes in the seventh week.
During stage HH16, Hey1 gene expression was maintained in the first three branchial clefts, the maxillary prominence primordium, the dorsal side of the mandibular prominence primordium, the ventral region of BA2 and BA3, the margins of the otic vesicle, and in the nasal placode
(Figure 1, D).
Interestingly, SU5402 treatment at E12.5 only results in narrower tooth bud formation, indicating that FGF signaling takes part in epithelium stratification but not placode
invagination [86, 87].
The cleft lip and palate defect occurs due to defect in the fusion of frontonasal, maxillary, and mandibular processes, while the proboscis lateralis occurs as a result of displacement of the nasal placode
during the formation of the nose [1, 2].
Further, Pax6 is specifically expressed in the lens placode
through a combination of activation by Sox2, Oct-1, and Foxe3 in the surface ectoderm and inhibition by TGF[beta] and Wnt signaling in the periocular neural crest [47-51].
Notably, the expression of Pax2 is one of the first indicators of otic placode
induction, and it continues to be expressed in various regions of the ear throughout subsequent stages of development.
Since the embryonic migration of GnRH neurons from the nasal placode
towards their final destination in the hypothalamus occurs in association with olfactory receptor neurons, the resulting phenotype includes anosmia in addition to HH.
At E2.5, we found that developing inner ear can be noticed by thickening of the ectodermal epithelium, otic placode
. Invagination of such placode
contributed to the otic cup closure and then the otic vesicle is completely formed (Brigande et al.; Sai & Ladher, 2015).
The main goal for prenatal repair of MMC is to achieve skin closure to prevent further damage of the placode
and arrest the CSF leak.
The genetic locus for X-linked Kallmann syndrome has been assigned to be X p 22.3, where the KAL-1 gene encodes Anosmin 1, which plays a role in normal migration of both GnRH secreting neurons and axons of olfactory neurons from the olfactory placode
to the brain, thus linking anosmia with hypogonadotropism.