Late Miocene hominin teeth from the Gona Paleoanthropological Research Project area, Afar, Ethiopia.

Since 2000, significant collections of Latest Miocene hominin fossils have been recovered from Chad, Kenya, and Ethiopia. These fossils have provided a better understanding of earliest hominin biology and context. Here, we describe five hominin teeth from two periods (ca. 5.4 Million-years-ago and ca. 6.3 Ma) that were recovered from the Adu-Asa Formation in the Gona Paleoanthropological Research Project area in the Afar, Ethiopia that we assign to either Hominina, gen. et sp. indet. or Ardipithecus kadabba. These specimens are compared with extant African ape and other Latest Miocene and Early Pliocene hominin teeth. The derived morphology of the large, non-sectorial maxillary canine and mandibular third premolar links them with later hominins and they are phenetically distinguishable and thus phyletically distinct from extant apes.

Early Pliocene hominids from Gona, Ethiopia.

Comparative biomolecular studies suggest that the last common ancestor of humans and chimpanzees, our closest living relatives, lived during the Late Miocene-Early Pliocene. Fossil evidence of Late Miocene-Early Pliocene hominid evolution is rare and limited to a few sites in Ethiopia, Kenya and Chad. Here we report new Early Pliocene hominid discoveries and their palaeoenvironmental context from the fossiliferous deposits of As Duma, Gona Western Margin (GWM), Afar, Ethiopia. The hominid dental anatomy (occlusal enamel thickness, absolute and relative size of the first and second lower molar crowns, and premolar crown and radicular anatomy) indicates attribution to Ardipithecus ramidus. The combined radioisotopic and palaeomagnetic data suggest an age of between 4.51 and 4.32 million years for the hominid finds at As Duma. Diverse sources of data (sedimentology, faunal composition, ecomorphological variables and stable carbon isotopic evidence from the palaeosols and fossil tooth enamel) indicate that the Early Pliocene As Duma sediments sample a moderate rainfall woodland and woodland/grassland.

Co-occurrence of Acheulian and Oldowan artifacts with Homo erectus cranial fossils from Gona, Afar, Ethiopia.

Although stone tools generally co-occur with early members of the genus Homo, they are rarely found in direct association with hominins. We report that both Acheulian and Oldowan artifacts and Homo erectus crania were found in close association at 1.26 million years (Ma) ago at Busidima North (BSN12), and ca. 1.6 to 1.5 Ma ago at Dana Aoule North (DAN5) archaeological sites at Gona, Afar, Ethiopia. The BSN12 partial cranium is robust and large, while the DAN5 cranium is smaller and more gracile, suggesting that H. erectus was probably a sexually dimorphic species. The evidence from Gona shows behavioral diversity and flexibility with a lengthy and concurrent use of both stone technologies by H. erectus, confounding a simple "single species/single technology" view of early Homo.

Apoptosis-inducing factor is a key factor in neuronal cell death propagated by BAX-dependent and BAX-independent mechanisms.

Mitochondria release proteins that propagate both caspase-dependent and caspase-independent cell death pathways. AIF (apoptosis-inducing factor) is an important caspase-independent death regulator in multiple neuronal injury pathways. Presently, there is considerable controversy as to whether AIF is neuroprotective or proapoptotic in neuronal injury, such as oxidative stress or excitotoxicity. To evaluate the role of AIF in BAX-dependent (DNA damage induced) and BAX-independent (excitotoxic) neuronal death, we used Harlequin (Hq) mice, which are hypomorphic for AIF. Neurons carrying double mutations for Hq/Apaf1-/- (apoptosis proteases-activating factor) are impaired in both caspase-dependent and AIF-mediated mitochondrial cell death pathways. These mutant cells exhibit extended neuroprotection against DNA damage, as well as glutamate-induced excitotoxicity. Specifically, AIF is involved in NMDA- and kainic acid- but not AMPA-induced excitotoxicity. In vivo excitotoxic studies using kainic acid-induced seizure showed that Hq mice had significantly less hippocampal damage than wild-type littermates. Our results demonstrate an important role for AIF in both BAX-dependent and BAX-independent mechanisms of neuronal injury.

A cell-autonomous requirement for the cell cycle regulatory protein, Rb, in neuronal migration.

Precise cell cycle regulation is critical for nervous system development. To assess the role of the cell cycle regulator, retinoblastoma (Rb) protein, in forebrain development, we studied mice with telencephalon-specific Rb deletions. We examined the role of Rb in neuronal specification and migration of diverse neuronal populations. Although layer specification occurred at the appropriate time in Rb mutants, migration of early-born cortical neurons was perturbed. Consistent with defects in radial migration, neuronal cell death in Rb mutants specifically affected Cajal-Retzius neurons. In the ventral telencephalon, although calbindin- and Lhx6-expressing cortical neurons were generated at embryonic day 12.5, their tangential migration into the neocortex was dramatically and specifically reduced in the mutant marginal zone. Cell transplantation assays revealed that defects in tangential migration arose owing to a cell-autonomous loss of Rb in migrating interneurons and not because of a defective cortical environment. These results revealed a cell-autonomous role for Rb in regulating the tangential migration of cortical interneurons. Taken together, we reveal a novel requirement for the cell cycle protein, Rb, in the regulation of neuronal migration.