α3Na+/K+-ATPase Deficiency Causes Brain Ventricle Dilation and Abrupt Embryonic Motility in Zebrafish

Distinct neurological disorders with ATP1A3 mutations

“…C. Atp1a3a / b knockdown zebrafish. Knockdown of Atp1a3a or Atp1a3b RNA transcript by ~65% in 60 hpf embryos had similar phenotypic effects 85 .…”

“…Similarly, Atp1a3a mRNA did not cross-rescue the phenotype of Atp1a3b -KD embryos. Both morphants display abnormal spontaneous motility and an abnormal response to tactile stimulation with a needle, 85 suggesting that both α3 paralogues are required for embryonic motility.…”

The Expanding Spectrum of Neurological Phenotypes in Children With ATP1A3 Mutations, Alternating Hemiplegia of Childhood, Rapid-onset Dystonia-Parkinsonism, CAPOS and Beyond

“…Critical function in maintaining ionic homeostasis has stage-specific developmental impact 43 ; however, the role of stress in protein expression and function is unclear. Other channelopathies have similar associations of disrupted membrane function with provoking stimulus, as in variants of FHM.…”

“…47 The relative infrequency of seizures reported in RDP and the variable epilepsy burden in AHC further highlights the likely contribution of age and developmentally specific protein expression. 43 …”

Local and long-range endogenous resting potential gradients antagonistically regulate apoptosis and proliferation in the embryonic CNS

“…Embryonic central nervous system (CNS) development is an ideal context in which to explore and understand the signals responsible for achieving the necessary target morphology. Developmental mispatterning is the cause of debilitating disorders, such as spina bifida (unclosed neural tube) (Copp andGreene, 2010, Detrait et al, 2005), anencephaly (small brain) (Copp and Greene, 2010, Detrait et al, 2005, Wallingford, 2006 and also increased susceptibility to degenerative disorders like Parkinson's, Alzheimer's, and autism (Doganli et al, 2013, Goldman et al, 2013, Pratt and Khakhalin, 2013. Hence, understanding how large-scale patterning of the brain normally occurs is a pre-requisite for major biomedical breakthroughs addressing birth defects and repairing injuries.…”