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Review
. 2004 Mar;204(Pt 3):151-63.
doi: 10.1111/j.0021-8782.2004.00278.x.

Perspectives on hyperphalangy: patterns and processes

Tim J Fedak  1 , Brian K Hall
Affiliations
Review

Perspectives on hyperphalangy: patterns and processes

Tim J Fedak et al. J Anat. 2004 Mar.

Abstract

Hyperphalangy is a digit morphology in which increased numbers of phalanges are arranged linearly within a digit beyond the plesiomorphic condition. We analyse patterns and processes of hyperphalangy by considering previous definitions and occurrences of hyperphalangy among terrestrial and secondarily aquatic extant and fossil taxa (cetaceans, ichthyosaurs, plesiosaurs and mosasaurs), and recent studies that elucidate the factors involved in terrestrial autopod joint induction. Extreme hyperphalangy, defined as exceeding a threshold condition of 4/6/6/6/6, is shown only to be found among secondarily aquatic vertebrates with a flipper limb morphology. Based on this definition, hyperphalangy occurs exclusively in digits II and III among extant cetaceans. Previous reports of cetacean embryos having more phalanges than adults is clarified and shown to be based on cartilaginous elements not ossified phalanges. Developmental prerequisites for hyperphalangy include lack of cell death in interdigital mesoderm (producing a flipper limb) and maintenance of a secondary apical ectodermal ridge (AER), which initiates digit elongation and extra joint patterning. Factors of the limb-patterning pathways located in the interdigital mesoderm, including bone morphogenetic proteins (BMPs), BMP antagonists, fibroblast growth factors (FGFs), growth/differentiation factor-5 (GDF-5), Wnt-14 and ck-erg, are implicated in maintenance of the flipper limb, secondary AER formation, digit elongation and additional joint induction leading to hyperphalangy.

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Figures

Fig. 1
Fig. 1
Diagrammatic right forelimbs in anterior view. (A) From proximal to distal, the tetrapod limb is composed of the stylopodium, zeugopodium, mesopodium, metapodium (grey shading) and phalanges. Together, the metapodium and phalanges are referred to as the autopodium. Shown here is a typical mammalian autopod with the phalangeal formula 2/3/3/3/3. Other theoretical limbs demonstrate (B) hyperphalangy (digits III–IV), (C) polyphalangy (digits III and IV), and (D) a polydactalous autopod with one extra digit.
Fig. 2
Fig. 2
(A) The right forelimb of a cat exhibits the typical terrestrial mammalian phalangeal formula 2/3/3/3/3. (B) The pentadactyl limb evolved probably from an ancestral eight-digit ancestor similar to Acanthostega, which shows a phalangeal formula 3/3/3/4/5/5/5/4. The mesopodial elements (carpals) are not known in the ancestral tetrapod Acanthostega, they were presumably cartilaginous and did not fossilize. A – modified from Liem et al. (2001), B – modified from Coates & Clack (1990).
Fig. 3
Fig. 3
Left forelimbs of Ichthyosaurus (A), the Sauropterygian Plesiosaurus brachpterygius (B) and the Mosasaurid Plotosaurus (C), demonstrating extreme hyperphalangy. The arrows (A) identify a polyphalangeous (branched) digit. Limbs are not drawn to scale. Abbreviations: h – humerus, r – radius, u – ulna. A – modified from Motani (1999), B – modified from Caldwell (1997b), C – modified from Carroll (1988).
Fig. 4
Fig. 4
The pes of the archaeoctye Rodhocetus balochistanensis (A); arrows show lateral and medial processes on distal phalanges (scale bar = 5 cm). The left forelimb of the round headed dolphin, Globicephala melas (B). The stippling represents cartilage; scale bar = 10 cm. A – modified from Gingerich et al. (2001), B – modified from Flower (1876).
Fig. 5
Fig. 5
Phylogenetic distribution of hyperphalangy in cetaceans, in which hyperphalangy is defined as exceeding the threshold of 4/6/6/6/6 (see text). The ACCTRAN analysis suggests hyperphalangy occurred three times (solid dots), with two reversals (open circles), and only ever involves the central digits II, III and IV.
Fig. 6
Fig. 6
FGFs are important signalling factors for limb and digit elongation. (A) A schematic diagram of an early right limb bud in dorsal view shows FGFs from the AER maintain the underlying mesenchymal cells and participate in the maintenance of the ZPA on the posterior distal margin of the limb. BMP antagonism (Gremlin) prevents BMP-induced regression of the AER and therefore maintains the Shh and FGF feedback loop. (B) At stage 30 FGF-8 (thick black line) is broadly expressed across the AER, but diminishes above the interdigital areas (id 1–3) at stage 32 (C). At stage 33, FGF-8 expression ceases above the digits in an order that corresponds with the (increasing) number of phalanges in each digit (D). B–D represent the right foot of a chick in dorsal view; redrawn from Gañan et al. (1998).
Fig. 7
Fig. 7
The autopod patterning pathway (A) shows the importance of BMPs and BMP antagonist interactions as well as the competitive interactions between BMPs and FGFs for the development of hyperphalangy (B). Antagonism of BMP factors could limit BMP induction of interdigital cell death (1), block BMP regression of the AER to prolong FGF expression and result in elongate anlagen (2), and to play a role in joint development by preventing BMP down-regulation of transcription factors such as ck-erg (3). Initially ck-erg is found along the entire anlagen, but becomes down-regulated by BMP-7, which is limited to areas of presumptive phalanges. Following joint induction, Wnt-14 and Gdf-5 are expressed in developing joints, while Indian hedgehog (Ihh) is up-regulated in phalanges and promotes bone development. A hypothesized explanation for the development of polyphalangy (C) suggests BMPs increase the radial diameter (double arrow) of an elongating anlagen to such a point that it becomes influenced by multiple FGF-8 signals from the AER (arrows), causing the anterior and posterior distal tip to expand in different directions (dashed lines).
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