Table 1 XP-CLR CDR genes with evidenced or putative roles in nervous system and neural crest pathways

RAI1

XP 52 (1st)

Xenopus

Mutants display craniofacial defects, improper migration of neural crest cells, decrease in facial cartilage components, axonal defects, and altered forebrain ventricle sizes [119].

NKAIN2 (TCBA1)

XP 9 (4th)

Human

Neurocristopathy-like phenotypes observed in patients with translocation breakpoint in NKAIN2 such as hair hypopigmentation, craniofacial and limb malformation, misdevelopment of eyes, and macrocephaly [172].

RNPC3

XP 57 (8th)

Human

Mutations linked to isolated growth hormone deficiency and pituitary hypoplasia [128].

NPR2

XP 127 (14th)

Human, mouse

Mutants exhibit dwarfism and impacted skeletal growth during embryogenesis [173, 174].

NPHP3

XP 197 (24th)

Mouse, xenopus

Left/right asymmetry, shortened body axes, and neural folds fail to close in mutants. Interacts with non-canonical Wnt pathway [84].

LIMCH1

XP 135 (30th)

Human

Significantly altered methylation patterns in Chinese Han pedigrees exhibiting neural tube defects [175]. LIMCH1 depletion increased cell migration by spatiotemporally regulating non-muscular myosin II activity [176].

CCDC65

XP 215 (45th)

Zebrafish

Critical for cilia and dynein function. Knockdowns cause left-right asymmetry and axis curvature embryos [177].

DAND5 (cerberus-like)

XP 177 (51st)

Mouse

Prevents signaling of the Nodal pathway on the right side of the developing mouse embryo, establishing left/right asymmetry during early somitogenesis [178].

GBF1

XP 220 (67th)

Fly

Expressed in embryogenesis, contributes to cell polarity in tubular organs and chemotaxis of neutrophils [179, 180].

GDPD5

XP 181 (102nd)

Zebrafish

Regulator of the notch signaling pathway, essential for neural crest pathway, linked to body axis determination [181], is induced by retinoids and drives motor neuron differentiation [182].

HAUS3

XP 38 (111th)

Zebrafish

Essential regulator of embryonic hematopoietic stem/progenitor cell maintenance and cell cycle progression [183].

PAX9

XP 80 (114th)

Mouse

Mutants displayed improper craniofacial development, lacked organs deriving from pharyngeal pouches, no teeth [184].

DIAPH1

XP 21 (117th)

Human

Expressed in neural progenitors, linked to microcephaly in humans [185], impacts migration of glioma cells [186].

TCF4

XP 3 (127th)

Mouse

Myelinates oligodendrocytes, antagonizes the Wnt signaling pathway, and interacts with SOX10 (a known neural crest gene [187]) to promote oligodendrocytic maturation gene expression [188].

TSPAN14

XP 46 (129th)

Human

Promotes the activity of notch receptors and the expression of ADAM10 [189], both players in the neural crest signaling pathway [190].

SATB2

XP 244 (131st)

Mouse

Mutants exhibit craniofacial abnormalities (e.g., cleft palate, dental misgrowth) and disrupted osteoblast differentiation [99].

FOXI1

XP 49 (136th)

Zebrafish

Regulates inner ear and jaw development in embryogenesis, and hypothesized to influence neural crest cell migration and/or separation in the brachial arches [191].

PRKCAB

XP 61 (138th)

Mouse

Mutations yield improper development of the neural tube and spina bifida in mice, asymmetric expansion of hedgehog signaling in the neural tube, impact neuronal cell survival [192].

GNAQ

XP 16 (141st)

Mouse

Mutants exhibit heart malformations and shortened jaws [193].

Tlx3

XP 48 (146th)

Mouse

Dorsal spinal cord development, specification of glutamatergic neurons [194], and is a target of Wnt signaling pathway [59].

SEMA4A

XP 70 (150th)

Xenopus

Expressed in neurogenic placodes in the developing neural tube, which along with neural crest cells, migrate to final cell locations [195].

TIAM1

XP 225 (154th)

Mouse

With PAR3, gene is responsible for determination of front-rear and apical-basal polarity in migratory keratinocyte cells [196].

PITX1

XP 124 (157th)

Mouse, anolis

Transcription factor whose binding sites are near key neural crest signaling members (Wnt, Hedgehog, BMP) [197]. Mutants have improper hind limb development and patterning as well as craniofacial abnormalities [100].

FKBP8

XP 175 (167th)

Mouse

Critical for development of the neural tube, establishes dorso-ventral patterning, and prevents apoptosis in embryonic cells in the neural tube [198].

AMBRA1

XP 161 (169th)

Mouse

Mutants show disrupted embryonic development, neural tube defects, cell cycle perturbations (unbalanced proliferation and high apoptosis) [199].

SCUBE1

XP 115 (202nd)

Mouse

Required for proper development of the central nervous system, neural tube, brain regions, and the cranial vault formation [200].

CYP1B1

XP 152 (229th)

Zebrafish

Mutants showed disrupted neural crest migration [201] and is associated with retinoic acid synthesis during the patterning of the developing embryo [50].