Deciphering the Forebrain Disorder in a Chicken Model of Cerebral Hernia

Abstract

Cerebral hernia in crested chicken has been characterized as the protrusion of cerebral hemispheres into the unsealed skull for hundreds of years, since Charles Darwin. The development of deformed forebrain (telencephalon) of cerebral hernia remains largely unknown. Here, the unsealed frontal skull combined with misplaced sphenoid bone was observed and potentially associated with brain protuberance. The shifted pallidum, elongated hippocampus, expanded mesopallium and nidopallium, and reduced hyperpallium were observed in seven regions of the malformed telencephalon. The neurons were detected with nuclear pyknosis and decreased density. Astrocytes showed uneven distribution and disordered protuberances in hyperpallium and hippocampus. Transcriptome analyses of chicken telencephalon (cerebral hernia vs. control) revealed 547 differentially expressed genes (DEGs), mainly related to nervous system development, and immune system processes, including astrocyte marker gene GFAP, and neuron and astrocyte developmental gene S100A6. The upregulation of GFAP and S100A6 genes in abnormal telencephalon was correlated with reduced DNA methylation levels in the promoter regions. The morphological, cellular, and molecular variations in the shape, regional specification, and cellular states of malformed telencephalon potentially participate in brain plasticity and previously reported behavior changes. Chickens with cerebral hernia might be an interesting and valuable disease model to further explore the recognition, diagnosis, and therapy of cerebral hernia development of crested chickens and other species.

Chicken HOXC8 and HOXC10 genes may play a role in the altered skull morphology associated with the Crest phenotype

“…This suggests the possibility that some relationships exist between the form of feather crest and the extent of skull protuberance. In addition, according to Li et al (2021), HOXC8 was expressed in the cranial area in several crested chicken breeds, including the Polish chicken, which had been shown to have a misplaced sphenoid bone (Tao et al, 2020) and a more loosely packed brain compared with WT chicken breeds (Frahm & Rehkämper, 1998). Furthermore, HOXC8 was also found in the cranial area of the Chinese crested duck, which expresses a crest cushion formed by fat tissues along with the feather crest in the caudal region of the head (Yuan et al, 2019).…”

“…Until a few decades ago, researchers could only conclude that cerebral hernia always exists along with a feather crest, but is not a necessary factor for the feather crest to exist (Fisher, 1935; Yoshimura et al, 2012). Specifically, the inheritance of the feather crest is autosomally recessive, while cerebral hernia is autosomally incompletely dominant (Davenport, 1906; Tao et al, 2020). Candidate causative genetic factors had not been identified until Y. Wang et al (2012) mapped it onto the GalGal3 assembly and discovered that ectopic expression of HOXC8 in the head was probably responsible for the phenotype (Y. Wang et al, 2012).…”

“…Moreover, no clear association of three reported Crest markers, HOXC8‐SSR , HOXC8‐3end , and HOXC8‐INTR , was found in Swiss crested chickens, and no polymorphisms were found in exons of HOXC8 (Joller et al, 2018). In addition, Tao et al (2020) suggested that a series of differentially expressed genes (DEGs) existed between crested and noncrested chicken brain regions and eventually identified 547 DEGs, including HOXC10 (Tao et al, 2020). Recently, a study using the GalGal6 assembly showed that the phenotype was actually caused by a 195 bp duplication in the intron of HOXC10 (Li et al, 2022).…”

“…Specifically, the inheritance of the feather crest is autosomally recessive, while cerebral hernia is autosomally incompletely dominant (Davenport, 1906;Tao et al, 2020). Candidate causative genetic factors had not been identified until Y.…”

The Effects of Domestication on the Brain and Behavior of the Chicken in the Light of Evolution

“…Another example is the spotted rabbit; special coloring is associated with a megacolon syndrome (Hirschsprung's disease) in homozygous spotted rabbits [Bödeker et al, 1995]. Furthermore, studying crested chickens and ducks provides insights into phenomena like encephaloceles and hydrocephalus [Tao et al, 2020].…”