A reverse genetic approach to test functional redundancy during embryogenesis.

Gene function during embryogenesis is typically defined by loss-of-function experiments, for example by targeted mutagenesis (knockout) in the mouse. In the zebrafish model, effective reverse genetic techniques have been developed using microinjection of gene-specific antisense morpholinos. Morpholinos target an mRNA through specific base-pairing and block gene function transiently by inhibiting translation or splicing for several days during embryogenesis (knockdown).

A forward chemical screen in zebrafish identifies a retinoic acid derivative with receptor specificity.

Background: Retinoids regulate key developmental pathways throughout life, and have potential uses for differentiation therapy. It should be possible to identify novel retinoids by coupling new chemical reactions with screens using the zebrafish embryonic model.

Principal Findings: We synthesized novel retinoid analogues and derivatives by amide coupling, obtaining 80-92% yields.