Detailed examples of how hierarchical assemblages of modules change over time are few. We found broadly conserved phylogenetic patterns in the directions of development within the median fins of fishes. From these, we identify four modules involved in their positioning and patterning. The evolutionary sequence of their hierarchical assembly and secondary dissociation is described. The changes in these modules during the evolution of fishes appear to be produced through dissociation, duplication and divergence, and co-option. Although the relationship between identified median fin modules and underlying mechanisms is unclear, Hox addresses may be correlated. Comparing homologous gene expression and function in various fishes may test these predictions.The earliest actinopterygians likely had dorsal and anal fins that were symmetrically positioned via a positioning module. The common patterning (differentiation) of skeletal elements within the dorsal and anal fins may have been set into motion by linkage to this positioning module. Frequent evolutionary changes in dorsal and anal fin position indicate a high level of dissociability of the positioning module from the patterning module. In contrast, the patterning of the dorsal and anal fins remains linked: In nearly all fishes, the endo- and exoskeletal elements of the two fins co-differentiate. In all fishes, the exoskeletal fin rays differentiate in the same directions as the endoskeletal supports, indicating complete developmental integration. In acanthopterygians, a new first dorsal fin module evolved via duplication and divergence. The median fins provide an example of how basic modularity is maintained over 400 million years of evolution.

Glutamatergic neurotransmission governs excitatory signaling in the mammalian brain, and abnormalities of glutamate signaling have been shown to contribute to both epilepsy and hyperkinetic movement disorders. The etiology of many severe childhood movement disorders and epilepsies remains uncharacterized. We describe a neurological disorder with epilepsy and prominent choreoathetosis caused by biallelic pathogenic variants in FRRS1L, which encodes an AMPA receptor outer-core protein. Loss of FRRS1L function attenuates AMPA-mediated currents, implicating chronic abnormalities of glutamatergic neurotransmission in this monogenic neurological disease of childhood.

Timing and pattern of expression of ten candidate segmentation genes or gene pairs were reviewed or examined in developing median fins of late-stage zebrafish, Danio rerio. We found a general correspondence in timing and pattern of expression between zebrafish fin radial segmentation and tetrapod joint development, suggesting that molecular mechanisms underlying radial segmentation have been conserved over 400 million years of evolution. Gene co-expression during segmentation (5.5-6.5 mm SL) is similar between tetrapods and zebrafish: bmp2b, bmp4, chordin, and gdf5 in interradial mesenchyme and ZS; bapx1, col2a1, noggin3, and sox9a in chondrocytes. Surprisingly, wnt9a is not expressed in the developing median fins, though wnt9b is detected. In contrast to all other candidate segmentation genes we examined, bapx1 is not expressed in the caudal fin, which does not segment. Together, these data suggest a scenario of gene interactions underlying radial segmentation based on the patterns and timing of candidate gene expression. Developmental Dynamics 236:3111-3128, 2007.

The dynamic expression of Gdf5 is described in the developing skeleton of the median fins of late-stage zebrafish, Danio rerio (6-45 days post-fertilization). In situ hybridization revealed expression in the mesenchyme between cartilage condensations of the endoskeletal supports of the dorsal, anal, and caudal fins. As development proceeds, the expression domains expand distally to surround tips of developing cartilages, consistent with a role in cartilage growth and differentiation. Gdf5 is later expressed in the segmenting regions of the dorsal and anal fin radials, which may indicate a role in segmentation. After growth to 7.5 mm, Gdf5 transcripts can no longer be detected in any of the median fins, nor is Gdf5 expression reinitiated in later development of the median fin skeleton.

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