Pathogenesis of holoprosencephaly
Xin Geng, Guillermo Oliver
Xin Geng, Guillermo Oliver
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Science in Medicine

Pathogenesis of holoprosencephaly

Abstract

Holoprosencephaly (HPE), the most common human forebrain malformation, occurs in 1 in 250 fetuses and 1 in 16,000 live births. HPE is etiologically heterogeneous, and its pathology is variable. Several mouse models of HPE have been generated, and some of the molecular causes of different forms of HPE and the mechanisms underlying its variable pathology have been revealed by these models. Herein, we summarize the current knowledge on the genetic alterations that cause HPE and discuss some important questions about this disease that remain to be answered.

Authors

Xin Geng, Guillermo Oliver

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Figure 1

Development of the mammalian forebrain.

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Development of the mammalian forebrain. (A–C) At early primitive-streak ...
(A–C) At early primitive-streak stage, epiblast cells ingress through the primitive streak (PS) to form the mesoderm. Medial sagittal section of E6.5 mouse (A) and Carnegie Stage 7 (CS7) human (B) embryos with anterior to the left. (C) Dorsal view of a CS7 human embryo. AVE, anterior visceral endoderm; VE, visceral endoderm. (D) At early somite stage (E8.5 for mouse; CS10 for human), the neural ectoderm has been specified into different regions along the anterior-posterior axis and the axial mesoderm is underlying the midline of the neural ectoderm. ANC, anterior notochord; PFB, prospective forebrain (or ANE); PH, prospective hindbrain; PM, prospective midbrain; PNC, posterior notochord; PSC, prospective spinal chord. (E) Neural tube closure occurs at around the 15-somite stage (E9.0 for mouse; CS11 for human). The forebrain gets further regionalized into telencephalon, diencephalon, and prospective hypothalamus (PH). OV, optic vesicle. (F) Approximately at E10.5 in the mouse or at CS14 in human embryos, the expanding telencephalon bifurcates dorsally to form the two hemispheres and gets patterned into dorsal telencephalon (DT) and ventral telencephalon (VT). (G and I) Lateral views of adult mouse (G) and human brain (I). OB, olfactory bulb. Black dashed lines in G and I indicate the location of coronal sections shown in H and J. (H and J) Coronal sections of adult mouse (H) and human brain (J). BG, basal ganglia; CiC, cingulate cortex; CoC, corpus callosum; LV, lateral ventricle.